A microfluidic system for precisely reproducing physiological blood pressure and wall shear stress to endothelial cells.

To reproduce hemodynamic stress microenvironments of endothelial cells in vitro is of vital significance, by which one could exploit the quantitative impact of hemodynamic stresses on endothelial function and seek innovative approaches to prevent circulatory system diseases. Although microfluidic technology has been regarded as an effective method to create physiological microenvironments, a microfluidic system to precisely reproduce physiological arterial hemodynamic stress microenvironments has not been reported yet. In this paper, a novel microfluidic chip consisting of a cell culture chamber with on-chip afterload components designed by the principle of input impedance to mimic the global hemodynamic behaviors is proposed. An external feedback control system is developed to accurately generate the input pressure waveform. A lumped parameter hemodynamic model (LPHM) is built to represent the input impedance to mimic the on-chip global hemodynamic behaviors. Sensitivity analysis of the model parameters is also elaborated. The performance of reproducing physiological blood pressure and wall shear stress is validated by both numerical characterization and flow experiment. Investigation of intracellular calcium ion dynamics in human umbilical vein endothelial cells is finally conducted to demonstrate the biological applicability of the proposed microfluidic system.

Precise generation of dynamic biochemical signals by controlling the programmable pump in a Y-shaped microfluidic chip with a "christmas tree" inlet.

The generation of dynamic biochemical signals in a microfluidic control system is of importance for the study of the interaction between biological cells and their niches. However, most of microfluidic control systems are not able to provide dynamic biochemical signals with high precision and stability due to inherent mechanical vibrations caused by the actuators of the programmable pumps. In this paper, we propose a novel microfluidic feedback control system integrating an external feedback control system with a Y-shaped microfluidic chip with a "Christmas tree" inlet. The Proportional Integral Derivative (PID) controller is implemented to reduce the influence of vibrations. In order to regulate the control parameters efficiently, a mathematical model is built to describe the actuator of the programmable pump, in which a fractional-order model is utilized. Both simulation and experimental studies are carried out, confirming that the microfluidic feedback control system can precisely and stably generate desired dynamic biochemical signals.

Fabricating a multi-component microfluidic system for exercise-induced endothelial cell mechanobiology guided by hemodynamic similarity.

Generating precise in vivo arterial endothelial hemodynamic microenvironments using microfluidics is essential for exploring endothelial mechanobiology. However, a hemodynamic principle guiding the fabrication of microfluidic systems is still lacking. We propose a hemodynamic similarity principle for quickly obtaining the input impedance of the microfluidic system in vitro derived from that of the arterial system in vivo to precisely generate the desired endothelial hemodynamic microenvironments. First, based on the equivalent of blood pressure (BP) and wall shear stress (WSS) waveforms, we establish a hemodynamic similarity principle to efficiently map the input impedance in vivo to that in vitro, after which the multi-component microfluidic system is designed and fabricated using a lumped parameter hemodynamic model. Second, numerical simulation and experimental studies are carried out to validate the performance of the designed microfluidic system. Finally, the intracellular Ca2+ responses after exposure to different intensities of exercise-induced BP and WSS waveforms are measured to improve the reliability of EC mechanobiological studies using the designed microfluidic system. Overall, the proposed hemodynamic similarity principle can guide the fabrication of a multi-component microfluidic system for endothelial cell mechanobiology.